Project Summary Eighty six million U.S. adults have prediabetes, and up to 75% of them will eventually develop diabetes. Landmark clinical trials have established that intensive lifestyle interventions (ILI) and metformin are safe and effective treatments to prevent or delay diabetes in adults with prediabetes and overweight/obesity. Despite being included in expert clinical guidelines, these treatments are rarely used and few studies have explored how to promote their uptake in practice. One possible approach for increasing adoption of ILI and metformin in primary care includes clinical decision support (CDS), which uses electronic systems to create tailored recommendations for evidence-based clinical care. While a large body of evidence demonstrates that CDS can improve the delivery of other recommended preventive services, this approach has not been definitively studied for ILI and metformin. We plan to address this critical knowledge gap by developing and evaluating the Prevent Diabetes Mellitus Clinical Decision Support (PreDM CDS) intervention for community health center patients with prediabetes and overweight/obesity. This novel CDS engages primary care providers and clinical staff to deliver the following intervention components: 1) a decision aid about diabetes prevention developed by our team; 2) an EHR referral to community-based ILI that meet recommended program requirements; and 3) a prompt for providers to consider prescribing metformin. Clinicians will receive monthly feedback about their use of the PreDM CDS through an existing dashboard. By accomplishing the following specific aims, this definitive R18 study will test the potential for CDS to promote diabetes prevention and weight loss efforts in primary care. In Aim 1, we will develop the proposed intervention by translating narrative guidelines about ILI and metformin into CDS, while incorporating extensive feedback from users. Aim 2 is a pragmatic cluster randomized trial, including 6 large community health center sites, which will examine the effectiveness of the PreDM CDS at inducing weight loss and improving other cardiometabolic markers. Aim 3 is a mixed-methods evaluation of the PreDM CDS, exploring its reach, adoption, implementation, maintenance, and cost. We hypothesize that the proposed PreDM CDS will increase patient's adoption of ILI and metformin, producing weight loss and improvements in other cardiometabolic markers. The resulting data, and an implementation toolkit created by the study team, will support the widespread dissemination of the PreDM CDS if found to be effective in the proposed study. Our proposal is responsive to PA-17-261 by: 1) developing new CDS that incorporates evidence-based guidelines for diabetes prevention that are infrequently used in current clinical practice; 2) evaluating the impact of the proposed CDS on patient outcomes, clinical workflows, healthcare process measures, adherence to guidelines, and costs; and 3) conducting this R18 study in a Health Center-Controlled Network that serves a minority- predominant population and has the capacity to disseminate the proposed PreDM CDS throughout its national network of community health centers serving 2 million patients.